We propose to synthesize, purify, and characterize new metal coordination complexes of the platinum group metals, and particularly platinum in the IV valence state, involving a variety of different substituted amine ligands and various leaving groups. We will isolate, purify, and characterize the monomer, trimer, dimer, and tetramer species of cis-diaquodiammineplatinum(II) and other analog molecules. We will study the chemistry of these structures and their equilibria in solution, their antitumor activity, their toxicities, and their interactions with nucleic acids. We will investigate the hypothesis that the formation of a bidentate, closed ring chelate of cis-dichlorodiammineplatinum(II) with the N7-06 sites of guanine can be the primary lesion on DNA initiating the anticancer activity. We will study the rates of repair and mechanisms of repair of this chelate complex in tumor and normal cells. We will synthesize, purify, and characterize platinum-pyrimidine blues formed with the monomer and oligomers of the diaquo species. The integrity of DNA in tumor cells in vivo treated with cis-dichlorodiammineplatinum(II) will be studied as a possible cause of "reproductive death" of the tumor cells. The accumulation of dimeric forms of the diaquo species in proximal convoluted tubules of the kidney will be studied as a possible cause of kidney toxicity. We will investigate the kinetics of tumor growth in vivo in treated and untreated animals to investigate the mechanisms of "reproductive death". We will study the surface charge of tumor and normal cells treated with various platinum drugs by electrophoretic mobility measurements.